Abstract
Combretastatin A-4 as the phosphate ester prodrug (3d) is a potent antineoplastic and antiangiogenesis substance and is in advanced preclinical development. For the purpose of improving the phosphorylation synthetic sequence from combretastatin A-4, new routes were investigated. The phosphorylation step was found to be considerably improved using in situ-generated dibenzyl chlorophosphite. Cleavage of the benzyl esters employing a trimethylchlorosilane/sodium iodide procedure, followed by treatment with sodium methoxide, led to the water-soluble prodrug (3d) in high yield.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 183-191 |
| Number of pages | 9 |
| Journal | Anti-Cancer Drug Design |
| Volume | 13 |
| Issue number | 3 |
| State | Published - Apr 1998 |
Keywords
- Antineoplastic agents
- Combretastatin A-4 prodrug
- Phosphate esters
ASJC Scopus subject areas
- Biochemistry
- Oncology
- General Biochemistry, Genetics and Molecular Biology
- Pharmacology
- Drug Discovery
- Organic Chemistry